Endogenous Purification Reveals GREB1 as a Key Estrogen Receptor Regulatory Factor
| Autor: | Wilbert Zwart, Aurélien A. Sérandour, John Stingl, Alan Atkins, Oscar M. Rueda, Jason S. Carroll, H. Raza Ali, Kelly A. Holmes, Carlos Caldas, Jessica L. L. Robinson, Amel Saadi, Carlo Palmieri, Gordon D. Brown, Caryn S. Ross-Innes, Clive D'Santos, Suraj Menon, Hisham Mohammed, Vasiliki Theodorou, Suet-Feung Chin |
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| Přispěvatelé: | Ali, Raza [0000-0001-7587-0906], Rueda Palacio, Oscar [0000-0003-0008-4884], Chin, Suet-Feung [0000-0001-5697-1082], Caldas, Carlos [0000-0003-3547-1489], Carroll, Jason [0000-0003-3643-0080], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Předmět: |
Chromatin Immunoprecipitation
Transcription Genetic Transplantation Heterologous Estrogen receptor Breast Neoplasms Mice SCID Biology Bioinformatics Interactome General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor Coactivator Animals Humans Protein Interaction Maps RNA Small Interfering lcsh:QH301-705.5 Transcription factor 030304 developmental biology Regulation of gene expression 0303 health sciences Estrogen Receptor alpha Chromatin 3. Good health Neoplasm Proteins Transplantation GREB1 Gene Expression Regulation Neoplastic lcsh:Biology (General) 030220 oncology & carcinogenesis Cancer research MCF-7 Cells Female RNA Interference Chromatin immunoprecipitation |
| Zdroj: | Cell Rep Cell Reports, Vol 3, Iss 2, Pp 342-349 (2013) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2013.01.010 |
| Popis: | Summary Estrogen receptor-α (ER) is the driving transcription factor in most breast cancers, and its associated proteins can influence drug response, but direct methods for identifying interacting proteins have been limited. We purified endogenous ER using an approach termed RIME ( r apid i mmunoprecipitation m ass spectrometry of e ndogenous proteins) and discovered the interactome under agonist- and antagonist-liganded conditions in breast cancer cells, revealing transcriptional networks in breast cancer. The most estrogen-enriched ER interactor is GREB1, a potential clinical biomarker with no known function. GREB1 is shown to be a chromatin-bound ER coactivator and is essential for ER-mediated transcription, because it stabilizes interactions between ER and additional cofactors. We show a GREB1-ER interaction in three xenograft tumors, and using a directed protein-protein approach, we find GREB1-ER interactions in half of ER + primary breast cancers. This finding is supported by histological expression of GREB1, which shows that GREB1 is expressed in half of ER + cancers, and predicts good clinical outcome. These findings reveal an unexpected role for GREB1 as an estrogen-specific ER cofactor that is expressed in drug-sensitive contexts. |
| Databáze: | OpenAIRE |
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